Detection and localization of calpain 3-like protease in a neuronal cell line: Possible regulation of apoptotic cell death through degradation of nuclear IκBα
| Autor: | Isabelle Clerc, Fabrice Raynaud, Anne Marcilhac, Yves Benyamin |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Programmed cell death
Proteases Muscle Proteins Apoptosis Hippocampus PC12 Cells Biochemistry Cell Line chemistry.chemical_compound NF-KappaB Inhibitor alpha Animals Annexin A5 Cell Nucleus Neurons biology Calpain Ionomycin NF-kappa B Cell Differentiation NF-κB Cell Biology Subcellular localization Rats Cell biology Enzyme Activation Isoenzymes Protein Transport IκBα chemistry Cytoplasm biology.protein I-kappa B Proteins Autolysis Protein Processing Post-Translational Fluorescein-5-isothiocyanate |
| Zdroj: | The International Journal of Biochemistry & Cell Biology. 38:2128-2140 |
| ISSN: | 1357-2725 |
| DOI: | 10.1016/j.biocel.2006.06.005 |
| Popis: | Calpains are a family of calcium-dependent cysteine proteases involved in major cellular processes including cell death. Their intracellular localization is essential to the understanding of their biological functions. In a previous confocal microscopy study, we observed the presence of a calpain 3-like protein in the mammalian brain. We thus first identified and confirmed the presence of a calpain 3-like protease in a neuronal cell model (NGF-differentiated PC12 cells). The goal of this study was to determine, for the first time in non-muscular cells, the relation between the subcellular localization, activation and function of this protease. We thus investigated its ability to regulate nuclear IkappaBalpha and therefore NF-kappaB activation after cell death stimulation. The IkappaBalpha/NF-kappaB signalling pathway indeed influences the neurodegenerative process by directly affecting gene expression in neurons. In the present study, we found that calpain 3 is present in the cytoplasm and nucleus of neuron-like PC12 cells and could be activated through autolysis in the nuclei of cells undergoing apoptosis after ionomycin treatment. Moreover, in these conditions, we demonstrated formation of the IkappaBalpha/calpain 3 complex and an increase in calpain-dependent IkappaBalpha cleavage products in cell nuclei. Stimulation of calpain-dependent cell death in neuron activated nuclear calpain 3-like protease and IkappaBalpha proteolysis resulted in the regulation of NF-kappaB activation. These data suggest a new mechanism by which calpain 3 activation is able to regulate the IkappaBalpha/NF-kappaB pathway and thus neurodegenerative processes. |
| Databáze: | OpenAIRE |
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